NO-Dependent Vasorelaxation Is Impaired After Gene Transfer of Inducible NO-Synthase

Carol A Gunnett; Donald D Lund; Yi Chu; Robert M Brooks; Frank M Faraci; Donald D Heistad

doi:10.1161/hq0801.093509

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NO-Dependent Vasorelaxation Is Impaired After Gene Transfer of Inducible NO-Synthase

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NO-Dependent Vasorelaxation Is Impaired After Gene Transfer of Inducible NO-Synthase

Carol A Gunnett, Donald D Lund, Yi Chu, Robert M Brooks, Frank M Faraci and Donald D Heistad

Arteriosclerosis, thrombosis, and vascular biology, Vol.21(8), pp.1281-1287

08/2001

DOI: 10.1161/hq0801.093509

PMID: 11498454

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Abstract

Proinflammatory stimuli produce expression of inducible NO-synthase (iNOS) within blood vessels and are associated with impaired endothelium-dependent relaxation. Gene transfer of iNOS was used to test the hypothesis that expression of iNOS in blood vessels produces impairment of NO-dependent relaxation as well as contraction. An adenoviral vector containing cDNA for murine iNOS, AdCMViNOS, and a control virus, AdCMVBglII, were used for gene transfer to rabbit carotid arteries in vitro and in vivo. After gene transfer of iNOS in vitro, contractile responses to KCl, phenylephrine, and U46619 were impaired. Relaxation in response to acetylcholine, ADP, A23187, and nitroprusside was also impaired. For example, maximum relaxation of vessels to acetylcholine (10 micromol/L) was 78+/-4% (mean+/-SE) after AdBglII (10(10.5) plaque-forming units) and 34+/-5% after AdiNOS (10(10.5) plaque-forming units, P<0.05). NO-independent relaxation in response to 8-bromo-cGMP and papaverine was not impaired after AdiNOS. Contraction and relaxation were improved in carotid arteries expressing iNOS by aminoguanidine and L-N-iminoethyl lysine, inhibitors of iNOS. After intraluminal gene transfer of iNOS in vivo, contraction of vessels in vitro was normal, but responses to acetylcholine were impaired. In summary, the major finding is that NO-dependent relaxation is impaired in arteries after gene transfer of iNOS in vitro and in vivo. Thus, expression of iNOS per se impairs NO-dependent relaxation.

Details

Title: Subtitle: NO-Dependent Vasorelaxation Is Impaired After Gene Transfer of Inducible NO-Synthase
Creators: Carol A Gunnett - From the Departments of Internal Medicine and Pharmacology, University of Iowa College of Medicine and VA Medical Center, Iowa City, Iowa
Donald D Lund - From the Departments of Internal Medicine and Pharmacology, University of Iowa College of Medicine and VA Medical Center, Iowa City, Iowa
Yi Chu - From the Departments of Internal Medicine and Pharmacology, University of Iowa College of Medicine and VA Medical Center, Iowa City, Iowa
Robert M Brooks - From the Departments of Internal Medicine and Pharmacology, University of Iowa College of Medicine and VA Medical Center, Iowa City, Iowa
Frank M Faraci - From the Departments of Internal Medicine and Pharmacology, University of Iowa College of Medicine and VA Medical Center, Iowa City, Iowa
Donald D Heistad - From the Departments of Internal Medicine and Pharmacology, University of Iowa College of Medicine and VA Medical Center, Iowa City, Iowa
Resource Type: Journal article
Publication Details: Arteriosclerosis, thrombosis, and vascular biology, Vol.21(8), pp.1281-1287
DOI: 10.1161/hq0801.093509
PMID: 11498454
NLM abbreviation: Arterioscler Thromb Vasc Biol
ISSN: 1079-5642
eISSN: 1524-4636
Language: English
Date published: 08/2001
Academic Unit: Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040547002771

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